We and others have shown that reduction of suppressor cell activity in mice by low doses of cytoxan or splenic irradiation can augment the immunogenicity of tumor vaccines, retard the growth of tumors and cause regression of tumors as large as 2.5 cm. Similar findings have resulted from administration of anti-suppressor T cell antibodies. Using assays measuring in vitro antibody response to sheep erythrocytes, we have demonstrated that lymphocytes from the majority of patients with Stage III or IV malignant melanoma respond poorly to antigens in vitro as a consequence of increased suppressor T-cell activity. We have also demonstrated significantly low MLC-\or Con A-induced suppressor cell response in the majority of patients with melanoma, breast cancer and colon cancer. On the basis of our results in experimental animals and with these assays of suppressor T-cell activity to guide us in patient selection and treatment evaluation, we propose to determine the agent(s), dose and treatment schedule producing optimal anti-suppressor cell effects in melanoma patients. Specifically, we propose to determine the effects of various single-\and multiple-dose regimens of cytoxan, splenic irradiation, anti-Leu-2 monoclonal antibody and combinations of these regimens on suppressor T-cell activity. If suppressor cell activity can be regularly decreased by one or more of these approaches, then therapeutic trials can be designed and the effect of anti-suppressor cell treatments on the immunogenicity of melanoma antigens in vaccines can be tested.